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Human Patient-Derived Brain Tumor Models to Recapitulate Ependymoma Tumor Vasculature

Despite in vivo malignancy, ependymoma lacks cell culture models, thus limiting therapy development. Here, we used a tunable three-dimensional (3D) culture system to approximate the ependymoma microenvironment for recapitulating a patient’s tumor in vitro. Our data showed that the inclusion of VEGF...

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Autores principales: Tang-Schomer, Min D., Bookland, Markus J., Sargent, Jack E., N. Jackvony, Taylor
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10376907/
https://www.ncbi.nlm.nih.gov/pubmed/37508868
http://dx.doi.org/10.3390/bioengineering10070840
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author Tang-Schomer, Min D.
Bookland, Markus J.
Sargent, Jack E.
N. Jackvony, Taylor
author_facet Tang-Schomer, Min D.
Bookland, Markus J.
Sargent, Jack E.
N. Jackvony, Taylor
author_sort Tang-Schomer, Min D.
collection PubMed
description Despite in vivo malignancy, ependymoma lacks cell culture models, thus limiting therapy development. Here, we used a tunable three-dimensional (3D) culture system to approximate the ependymoma microenvironment for recapitulating a patient’s tumor in vitro. Our data showed that the inclusion of VEGF in serum-free, mixed neural and endothelial cell culture media supported the in vitro growth of all four ependymoma patient samples. The growth was driven by Nestin and Ki67 double-positive cells in a putative cancer stem cell niche, which was manifested as rosette-looking clusters in 2D and spheroids in 3D. The effects of extracellular matrix (ECM) such as collagen or Matrigel superseded that of the media conditions, with Matrigel resulting in the greater enrichment of Nestin-positive cells. When mixed with endothelial cells, the 3D co-culture models developed capillary networks resembling the in vivo ependymoma vasculature. The transcriptomic analysis of two patient cases demonstrated the separation of in vitro cultures by individual patients, with one patient’s culture samples closely clustered with the primary tumor tissue. While VEGF was found to be necessary for preserving the transcriptomic features of in vitro cultures, the presence of endothelial cells shifted the gene’s expression patterns, especially genes associated with ECM remodeling. The homeobox genes were mostly affected in the 3D in vitro models compared to the primary tumor tissue and between different 3D formats. These findings provide a basis for understanding the ependymoma microenvironment and enabling the further development of patient-derived in vitro ependymoma models for personalized medicine.
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spelling pubmed-103769072023-07-29 Human Patient-Derived Brain Tumor Models to Recapitulate Ependymoma Tumor Vasculature Tang-Schomer, Min D. Bookland, Markus J. Sargent, Jack E. N. Jackvony, Taylor Bioengineering (Basel) Article Despite in vivo malignancy, ependymoma lacks cell culture models, thus limiting therapy development. Here, we used a tunable three-dimensional (3D) culture system to approximate the ependymoma microenvironment for recapitulating a patient’s tumor in vitro. Our data showed that the inclusion of VEGF in serum-free, mixed neural and endothelial cell culture media supported the in vitro growth of all four ependymoma patient samples. The growth was driven by Nestin and Ki67 double-positive cells in a putative cancer stem cell niche, which was manifested as rosette-looking clusters in 2D and spheroids in 3D. The effects of extracellular matrix (ECM) such as collagen or Matrigel superseded that of the media conditions, with Matrigel resulting in the greater enrichment of Nestin-positive cells. When mixed with endothelial cells, the 3D co-culture models developed capillary networks resembling the in vivo ependymoma vasculature. The transcriptomic analysis of two patient cases demonstrated the separation of in vitro cultures by individual patients, with one patient’s culture samples closely clustered with the primary tumor tissue. While VEGF was found to be necessary for preserving the transcriptomic features of in vitro cultures, the presence of endothelial cells shifted the gene’s expression patterns, especially genes associated with ECM remodeling. The homeobox genes were mostly affected in the 3D in vitro models compared to the primary tumor tissue and between different 3D formats. These findings provide a basis for understanding the ependymoma microenvironment and enabling the further development of patient-derived in vitro ependymoma models for personalized medicine. MDPI 2023-07-15 /pmc/articles/PMC10376907/ /pubmed/37508868 http://dx.doi.org/10.3390/bioengineering10070840 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tang-Schomer, Min D.
Bookland, Markus J.
Sargent, Jack E.
N. Jackvony, Taylor
Human Patient-Derived Brain Tumor Models to Recapitulate Ependymoma Tumor Vasculature
title Human Patient-Derived Brain Tumor Models to Recapitulate Ependymoma Tumor Vasculature
title_full Human Patient-Derived Brain Tumor Models to Recapitulate Ependymoma Tumor Vasculature
title_fullStr Human Patient-Derived Brain Tumor Models to Recapitulate Ependymoma Tumor Vasculature
title_full_unstemmed Human Patient-Derived Brain Tumor Models to Recapitulate Ependymoma Tumor Vasculature
title_short Human Patient-Derived Brain Tumor Models to Recapitulate Ependymoma Tumor Vasculature
title_sort human patient-derived brain tumor models to recapitulate ependymoma tumor vasculature
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10376907/
https://www.ncbi.nlm.nih.gov/pubmed/37508868
http://dx.doi.org/10.3390/bioengineering10070840
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